Cardiology

Butler, J., Anker, S.D., Filippatos, G., Khan, M.S., Ferreira, J.P., Pocock, S.J., Giannetti, N., Januzzi, J.L., Piña, I.L., Lam, C.S.P., Ponikowski, P., Sattar, N., Verma, S., Brueckmann, M., Jamal, W., Vedin, O., Peil, B., Zeller, C., Zannad, F. and Packer, M. (2021). “Empagliflozin and health-related quality of life outcomes in patients with heart failure with reduced ejection fraction: the EMPEROR-Reduced trial.” Eur Heart J Jan 9;ehaa1007. ]Epub ahead of print].

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AIMS: In this secondary analysis of the EMPEROR-Reduced trial, we sought to evaluate whether the benefits of empagliflozin varied by baseline health status and how empagliflozin impacted patient-reported outcomes in patients with heart failure with reduced ejection fraction. METHODS AND RESULTS: Health status was assessed by the Kansas City Cardiomyopathy Questionnaires-clinical summary score (KCCQ-CSS). The influence of baseline KCCQ-CSS (analyzed by tertiles) on the effect of empagliflozin on major outcomes was examined using Cox proportional hazards models. Responder analyses were performed to assess the odds of improvement and deterioration in KCCQ scores related to treatment with empagliflozin. Empagliflozin reduced the primary outcome of cardiovascular death or heart failure hospitalization regardless of baseline KCCQ-CSS tertiles [hazard ratio (HR) 0.83 (0.68-1.02), HR 0.74 (0.58-0.94), and HR 0.61 (0.46-0.82) for <62.5, 62.6-85.4, and ≥85.4 score tertiles, respectively; P-trend = 0.10]. Empagliflozin improved KCCQ-CSS, total symptom score, and overall summary score at 3, 8, and 12 months. More patients on empagliflozin had ≥5-point [odds ratio (OR) 1.20 (1.05-1.37)], 10-point [OR 1.26 (1.10-1.44)], and 15-point [OR 1.29 (1.12-1.48)] improvement and fewer had ≥5-point [OR 0.75 (0.64-0.87)] deterioration in KCCQ-CSS at 3 months. These benefits were sustained at 8 and 12 months and were similar for other KCCQ domains. CONCLUSION: Empagliflozin improved cardiovascular death or heart failure hospitalization risk across the range of baseline health status. Empagliflozin improved health status across various domains, and this benefit was sustained during long-term follow-up.

Anker, S.D., Butler, J., Filippatos, G., Khan, M.S., Marx, N., Lam, C.S.P., Schnaidt, S., Ofstad, A.P., Brueckmann, M., Jamal, W., Bocchi, E.A., Ponikowski, P., Perrone, S.V., Januzzi, J.L., Verma, S., Böhm, M., Ferreira, J.P., Pocock, S.J., Zannad, F. and Packer, M. (2021). “Effect of Empagliflozin on Cardiovascular and Renal Outcomes in Patients With Heart Failure by Baseline Diabetes Status: Results From the EMPEROR-Reduced Trial.” Circulation 143(4): 337-349.

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BACKGROUND: Sodium-glucose cotransporter 2 inhibitors improve outcomes in patients with heart failure with reduced ejection fraction, but additional information is needed about whether glycemic status influences the magnitude of their benefits on heart failure and renal events. METHODS: Patients with Class II-IV heart failure and a left ventricular ejection fraction ≤40% were randomized to receive empagliflozin (10 mg daily) or placebo in addition to recommended therapy. We prespecified a comparison of the effect of empagliflozin in patients with and without diabetes. RESULTS: Of the 3730 patients enrolled, 1856 (50%) had diabetes, 1268 (34%) had prediabetes (hemoglobin A1c [HbA1c] 5.7-6.4%), and 606 (16%) had normoglycemia (HbA1c <5.7%). The risks of the primary outcome (cardiovascular death or hospitalization for heart failure), total hospitalizations for heart failure, and adverse renal outcomes were higher in patients with diabetes, but were similar between patients with prediabetes and normoglycemia. Empagliflozin reduced the risk of the primary outcome in patients with and without diabetes (hazard ratio, 0.72 [95% CI, 0.60-0.87] and 0.78 [95% CI, 0.64-0.97], respectively, P-interaction=0.57). Patients with and without diabetes also did not differ with respect to the effect of empagliflozin on total hospitalizations for heart failure, on the decline in estimated glomerular filtration rate over time, and on the risk of serious adverse renal outcomes. Among these end points, the effects of the drug did not differ in patients with prediabetes or normoglycemia. When analyzed as a continuous variable, baseline HbA1c did not significantly modify the benefits of empagliflozin on the primary outcome (P-interaction=0.40). Empagliflozin did not lower HbA1c in patients with prediabetes or normoglycemia and was not associated with increased risk of hypoglycemia. CONCLUSIONS: In EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empagliflozin significantly improved cardiovascular and renal outcomes in patients with heart failure and a reduced ejection fraction, independent of baseline diabetes status and across the continuum of HbA1c.

Palazzuoli, A., Ruocco, G., Tecson, K.M. and McCullough, P.A. (2021). “Screening, detection, and management of heart failure in the SARS-CoV2 (COVID-19) pandemic.” Heart Fail Rev Jan 6;1-7. [ Epub ahead of print]. 1-7.

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Observational studies suggest that a heart failure (HF) diagnosis carries a poor prognosis in subjects with severe SARS-CoV2 (COVID-19) infection, but it is unknown whether this association reflects direct myocardial damage due to COVID-19 or the consequence of preexisting cardiac defects and related cardiovascular disease (CVD) risk burden. Although the close relation between CVD and COVID-19 outcomes is well established, contrasting data exists about the occurrence of HF complications during COVID-19 infection. Therefore, a specific algorithm focused on diagnostic differentiation in acute patients distinguishing between acute HF and acute respiratory distress syndrome related to COVID-19 is needed. Further, several concerns exist for the management of patients with an uncertain diagnosis and acute dyspnea, the exact relationship existing between COVID-19 and HF. Therefore, the treatment for subjects with both COVID-19 and HF and which criteria may be defined for domiciliary or hospital management, remain poorly defined. Herein, we describe practices to be adopted in order to address these concerns and avoid further virus spread among patients, l and their familiars involved in such patients’ care.

Wang, R., Takahashi, K., Garg, S., Thuijs, D., Kappetein, A.P., Mack, M.J., Morice, M.C., Mohr, F.W., Curzen, N., Davierwala, P., Milojevic, M., van Geuns, R.J., Head, S.J., Onuma, Y., Holmes, D.R., Jr. and Serruys, P.W. (2021). “Ten-year all-cause death following percutaneous or surgical revascularization in patients with prior cerebrovascular disease: insights from the SYNTAX Extended Survival study.” Clin Res Cardiol Jan 30. [ Epub ahead of print].

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BACKGROUND: Coronary bypass artery grafting (CABG) has a higher procedural risk of stroke than percutaneous coronary intervention (PCI), but may offer better long-term survival. The optimal revascularization strategy for patients with prior cerebrovascular disease (CEVD) remains unclear. METHODS AND RESULTS: The SYNTAXES study assessed the vital status out to 10 year of patients with three-vessel disease and/or left main coronary artery disease enrolled in the SYNTAX trial. The relative efficacy of PCI vs. CABG in terms of 10 year all-cause death was assessed according to prior CEVD. The primary endpoint was 10 year all-cause death. The status of prior CEVD was available in 1791 (99.5%) patients, of whom 253 patients had prior CEVD. Patients with prior CEVD were older and had more comorbidities (medically treated diabetes, insulin-dependent diabetes, metabolic syndrome, peripheral vascular disease, chronic obstructive pulmonary disease, impaired renal function, and congestive heart failure), compared with those without prior CEVD. Prior CEVD was an independent predictor of 10 year all-cause death (adjusted HR: 1.35; 95% CI: 1.04-1.73; p = 0.021). Patients with prior CEVD had a significantly higher risk of 10 year all-cause death (41.1 vs. 24.1%; HR: 1.92; 95% CI: 1.54-2.40; p < 0.001). The risk of 10 year all-cause death was similar between patients receiving PCI or CABG irrespective of the presence of prior CEVD (p(-interaction) = 0.624). CONCLUSION: Prior CEVD was associated with a significantly increased risk of 10 year all-cause death which was similar in patients treated with PCI or CABG. These results do not support preferential referral for PCI rather than CABG in patients with prior CEVD. TRIAL REGISTRATION: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.

Thourani, V.H., Edelman, J.J., Holmes, S.D., Nguyen, T.C., Carroll, J., Mack, M.J., Kapadia, S., Tang, G.H.L., Kodali, S., Kaneko, T., Meduri, C.U., Forcillo, J., Ferdinand, F.D., Fontana, G., Suwalski, P., Kiaii, B., Balkhy, H., Kempfert, J., Cheung, A., Borger, M.A., Reardon, M., Leon, M.B., Popma, J.J. and Ad, N. (2021). “The International Society for Minimally Invasive Cardiothoracic Surgery Expert Consensus Statement on Transcatheter and Surgical Aortic Valve Replacement in Low- and Intermediate-Risk Patients: A Meta-Analysis of Randomized and Propensity-Matched Studies.” Innovations (Phila) Jan 25;1556984520978316. [Epub ahead of print]. 1556984520978316.

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OBJECTIVE: There is an increasing amount of evidence supporting use of transcatheter aortic valve replacement (TAVR) for treatment of aortic stenosis in patients at low or intermediate risk for surgical aortic valve replacement (SAVR). TAVR is now approved for use in all patient cohorts. Despite this, there remains debate about the relative efficacy of TAVR compared with SAVR in lower-risk cohorts and various subgroups of patients. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and propensity-matched trials to guide a consensus among expert cardiologists and surgeons. METHODS: Studies comparing TAVR and SAVR in low- and intermediate-risk patients were identified by a thorough search of the major databases. Mortality, stroke, and other perioperative outcomes were assessed at 30 days and 1 year. RESULTS: Early mortality was lower in TAVR compared to SAVR in RCTs, but not propensity-matched studies in low-risk cohorts (0.66% vs 1.5%; odds ratio [OR] = 0.44, 95% confidence interval [CI] 0.20 to 0.98, I(2) = 0%). No difference in mortality between TAVR and SAVR was identified in intermediate-risk patients at early or later time points. Incidence of perioperative stroke in 3 low-risk RCTs was significantly lower in TAVR (0.4%) than SAVR (1.4%; OR = 0.33, 95% CI 0.13 to 0.81, I(2) = 0%). There was no difference in stroke for intermediate-risk patients between TAVR and SAVR. The expert panel of cardiologists and cardiac surgeons provided recommendations for TAVR and SAVR in various clinical scenarios. CONCLUSIONS: In RCTs comparing TAVR and SAVR in low-risk patients, early mortality and stroke were lower in TAVR, but did not differ at 1 year. There was no difference in mortality and stroke in intermediate-risk patients. The Multidisciplinary Heart Team must consider individual patient characteristics and preferences when recommending TAVR or SAVR. The decision must consider the long-term management of each patient’s aortic valve disease.